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Escitalopram Ameliorates Cognitive Impairment in D-Galactose-Injected Ovariectomized Rats: Modulation of JNK, GSK-3β, and ERK Signalling Pathways.

  • Ibrahim WW Department of Pharmacology & Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt. weam.wadie@pharma.cu.edu.eg.
  • Abdelkader NF Department of Pharmacology & Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
  • Ismail HM Department of Pharmaceutical Biochemistry, School of Pharmaceutical Sciences, University of Geneva, Geneva, Switzerland.
  • Khattab MM Department of Pharmacology & Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
  • 2019-07-13
Published in:
  • Scientific reports. - 2019
Animals
Antidepressive Agents, Second-Generation
Citalopram
Cognitive Dysfunction
Female
Galactose
Glycogen Synthase Kinase 3 beta
Humans
Learning
MAP Kinase Kinase 4
MAP Kinase Signaling System
Memory
Ovariectomy
Rats
Rats, Wistar
English Though selective serotonin reuptake inhibitors (SSRIs) have been found to increase cognitive performance in some studies on patients and animal models of Alzheimer's disease (AD), other studies have reported contradictory results, and the mechanism of action has not been fully described. This study aimed to examine the effect of escitalopram, an SSRI, in an experimental model of AD and to determine the involved intracellular signalling pathways. Ovariectomized rats were administered D-galactose (150 mg/kg/day, i.p) over ten weeks to induce AD. Treatment with escitalopram (10 mg/kg/day, p.o) for four weeks, starting from the 7th week of D-galactose injection, enhanced memory performance and attenuated associated histopathological changes. Escitalopram reduced hippocampal amyloid β 42, β-secretase, and p-tau, while increasing α-secretase levels. Furthermore, it decreased tumor necrosis factor-α, nuclear factor-kappa B p65, and NADPH oxidase, while enhancing brain-derived neurotrophic factor, phospho-cAMP response element binding protein, and synaptophysin levels. Moreover, escitalopram diminished the protein expression of the phosphorylated forms of c-Jun N-terminal kinase (JNK)/c-Jun, while increasing those of phosphoinositide 3-kinase (PI3K), protein kinase B (Akt), glycogen synthase kinase-3β (GSK-3β), extracellular signal-regulated kinase (ERK) and its upstream kinases MEK and Raf-1. In conclusion, escitalopram ameliorated D-galactose/ovariectomy-induced AD-like features through modulation of PI3K/Akt/GSK-3β, Raf-1/MEK/ERK, and JNK/c-Jun pathways.
Language
  • English
Open access status
gold
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Persistent URL
https://sonar.ch/global/documents/43730
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